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Novel Model of Calvarial Defect in an Infected Unfavorable Wound: Reconstruction With rhBMP-2. Part II

Kinsella, Christopher R. Jr MD*; Cray, James J. PhD*; Smith, Darren M. MD*; Rottgers, S. Alex MD*; Mooney, Mark P. PhD*†‡; Cooper, Gregory M. PhD*†§; Losee, Joseph E. MD, FACS, FAAP*

Journal of Craniofacial Surgery: March 2012 - Volume 23 - Issue 2 - p 410–414
doi: 10.1097/SCS.0b013e318240feb8
Original Articles

Background Animal models of bone reconstruction have shown recombinant human bone morphogenetic protein 2 (rhBMP-2) to be an effective therapy in the acute calvarial defect wound. The purpose of this study was to compare the effectiveness of rhBMP-2 in a rabbit model of an unfavorable scarred calvarial wound with the criterion standard of autograft.

Methods Nineteen adult New Zealand white rabbits underwent subtotal calvariectomy. After 6 weeks of healing and normal scar formation, these animals underwent reoperation for scar debridement and assignment to 1 of 4 therapeutic groups. Animals were assigned to an empty control group (no treatment, n = 3), vehicle control group (neutral buffered solution on an absorbable collagen sponge [ACS], n = 3), surgical control group (cryopreserved autograft, n = 3), or an experimental treatment group (rhBMP-2 on an ACS, n = 10). All animals underwent computed tomography imaging at 0, 2, 4, and 6 weeks after secondary reconstructive surgery. At 6 weeks, all animals were killed, and the defects were examined histologically. Percentage of healing of each defect was determined, and a 4 × 3 mixed-model analysis of variance was performed on healing as a function of time and therapy.

Results Based on measures of defect radiopacity, the treatment group (rhBMP-2/ACS) and surgical control group (autograft) were statistically equivalent with 98% and 83% healing, respectively, at 6 weeks. The empty control and vehicle control groups were inferior to the treatment group (rhBMP-2/ACS) and surgical control (autograft) groups at each timepoint (P < 0.05). Histologically, bone in the surgical control (autograft) group was less trabecular and less cellular than the bone formed in the experimental treatment group (rhBMP-2/ACS).

Conclusions Compared with historical controls, rhBMP-2 therapy was as effective in reconstructing calvarial defects in the unfavorable scarred wound as in the acute favorable calvarial wound. When compared with cryopreserved autograft, rhBMP-2–regenerated bone showed equal defect coverage and similar bone thickness with varying bony architecture.

From the *Division of Plastic Surgery and Departments of †Oral Biology, ‡Anthropology and Orthodontics, and §Bioengineering, University of Pittsburgh, Pittsburgh, PA.

Received April 12, 2011.

Accepted for publication July 10, 2011.

Address correspondence and reprint requests to Joseph E. Losee, MD, FACS, FAAP, Division Pediatric Plastic Surgery, Children’s Hospital of Pittsburgh of UPMC, Children’s Hospital Dr, 45th & Penn, Pittsburgh, PA 15201; E-mail:

This study was funded with an industry grant from Medtronic Inc, the makers of INFUSE (rhBMP-2/ACS).

The authors report no conflicts of interest.

© 2012 Mutaz B. Habal, MD